The JAK/STAT pathway involves cytokines binding to cell surface receptors which activates JAK kinases, leading to phosphorylation of STAT transcription factors. STAT dimers then enter the nucleus and regulate transcription of genes involved in processes like proliferation, differentiation, and survival. Disregulation of the JAK/STAT pathway contributes to diseases like leukemia, and JAK inhibitors have been developed for leukemia therapy.

1. Janus Kinase/Signal Transducers and
Activators of Transcription (JAK/STAT)
signaling pathway

2. • JAK- Family of cytoplasmic non-receptor
tyrosine kinases which get activated after
the binding of a cytokine to the cell-surface
cytokine receptor.
• STAT- Family of transcription factors that
become activated when one of the tyrosine
residues is phosphorylated by JAK.
• STAT3 dimers then translocate from the
cytoplasm into the nucleus – bind to
Interferon-stimulated Response Elements.
• Cellular responses to dozens of cytokines
and growth factors are mediated by the
evolutionarily conserved.

4. • Ex: Involved in Ig class switching in B Cells
following a response to IL-4 which
phosphorylates STAT6.
• Resistance to viral infection by interferons
mediated through STAT1.
• Trans-phosphorylated JAKs then
phosphorylate downstream substrates,
including both the receptor and the STATs.
• Activated STATs enter the nucleus and
bind as dimers or as more complex
oligomers to specific enhancer sequences in
target genes, thus regulating their
transcription.

5. The JAK/STAT pathway
Harrison D A Cold Spring Harb Perspect Biol
2012;4:a011205
©2012 by Cold Spring Harbor Laboratory Press

6. • Responses include proliferation, differentiation,
migration, apoptosis, and cell survival.
• Essential for numerous developmental and
homeostatic processes, including hematopoiesis,
immune cell development, stem cell
maintenance, organismal growth, and mammary
gland development.
• Human JAK mutations cause numerous diseases,
including SCID, hyper IgE syndrome, certain
leukemias, polycythemia vera, and other
myeloproliferative disorders.
• Small molecular weight cell membrane-permeable
drugs that target this pathways have been
developed for leukemia therapy. (JAK Inhibitors)

7. • Responses include proliferation, differentiation,
migration, apoptosis, and cell survival.
• Essential for numerous developmental and
homeostatic processes, including hematopoiesis,
immune cell development, stem cell
maintenance, organismal growth, and mammary
gland development.
• Human JAK mutations cause numerous diseases,
including SCID, hyper IgE syndrome, certain
leukemias, polycythemia vera, and other
myeloproliferative disorders.
• Small molecular weight cell membrane-permeable
drugs that target this pathways have been
developed for leukemia therapy. (JAK Inhibitors)